The objective of this study is to better our understanding of the biosynthesis of vitamin B12 and its derivatives (corrinoids), and to find the role of folic acid compounds and methylcorrinoids in the synthesis of acetate from CO2 as occurs in some anaerobic bacteria. Our $oal is also to find the mechanisms of enzymes which catalyze the $eactions converting CO2 to acetate. The proposed study will be with Clostridium thermoaceticum and Clostridium formicoaceticum. These bacteria contain high levels of the enzymes, which catalyze the conversion of one-carbon derivatives of tetrahydrofolate and methylcorrinoids, which are intermediates in the synthesis of acetate from CO2. The following enzymes will be studied: formyltetrahydrofolate synthetase, methylenetetrahydrofolate dehydrogenase and methylenetetrahydrofolate reductase. Investigation will be done also of the mechanism of converting methyltetrahydrofolate to acetate, which may occur via a corrinoid-protein. Formate dehydrogenase from both bacteria reduces CO2 to formate. This enzyme needs selenium and tungsten for formation. The possiblility that these metals are part of the active site will be investigated using radioactive Se75 and W185. C. thermoaceticum as far is known synthesizes only the corrinoid and not the porphyrin types of tetrapyrroles. Cell free extracts of this bacterium catalyzes the formation of corrinoids from C14 delta- aminolevulinic acid and these extracts will be used to find intermediates and enzymes involved in the formation of corrinoids.